Somatic hypermutation is a regulated process that introduces single base changes in variable regions of antibody genes. Hypermutation can have distinct biological roles: it can diversify the immune repertoire or provide the means for production of high affinity antibodies. Hypermutation can also alter the DNA sequence of certain oncogenes, making this pathway important for understanding the mutagenic basis of cancer development. Multiple repair factors are involved in hypermutation. The specific aims of this proposal are to clarify activities important for hypermutation and elucidate the molecular mechanism of this process. In addition, identification of critical hypermutation molecules and their repair roles will provide new therapeutics that could enhance the efficiency of immunization and decrease the genomic instability associated with cancer. [unreadable] [unreadable]